How to protect yourself against malaria · PDF fileDorling D Worldmapper. PLoS Med 4 (1), 2007 4 | Mine Action Technology Workshop | 10 September 2008 GLOBAL MALARIA PROGRAMME Global

World Health Organization 17 September, 2008

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How to protect yourself against malariaHow to protect yourself against malaria

Mine Action Technology Workshop 2008

co-hosted by the United Nations Mine Action Service (UNMAS)

and the Geneva International Centre for Humanitarian Demining

Presented by Dr Andrea Bosman

Global Malaria Programme

Geneva, 10 September 2008

Mine Action Technology Workshop | 10 September 20082 |GLOBAL

MALARIA PROGRAMME

THE GLOBAL BURDEN OF MALARIA:

EVERY DAY MALARIA KILLS IN NUMBERS EQUIVALENT TO "9/11" TRAGEDY OF THE NEW YORK TWIN TOWERS


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MALARIA PROGRAMME

If malaria burden was proportional

to country surface areas …

If malaria If malaria burdenburden waswas proportionalproportional

to country surface areas to country surface areas ……

Dorling D Worldmapper. PLoS Med 4 (1), 2007


MALARIA PROGRAMME

Global malaria burdenGlobal malaria burden

� 4 species of malaria parasites infect people

– Plasmodium falciparum, P. vivax, P. malariae, P. ovale

� 247 million malaria patients per year

� Nearly 1 million deaths due to malaria per year

� 90% of deaths and 60% of cases occur in Africa south of the Sahara

� 109 malaria endemic countries/territories

– 15 countries with no P.falciparum transmission, only P.vivax

– 7 countries with recently no more locally transmitted cases


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Poor access to health care in the

Amazonas

MDRfalciparummalaria

Resurgence in Central Asia & Eastern Europe

Childhood dealths in

sub-Saharan Africa

Vast burden of morbidity & economic loss

The Global Malaria PictureThe Global Malaria Picture

EMRO INTERCOUNTRY MEETING, 1-4 June 20086 |GLOBAL

MALARIA PROGRAMME

Evolution of global malaria distribution

Mid 19th centuryMid 19th century 19451945

19771977 20072007

37 countries

freed from malaria

37 countries

freed from malaria

Sweden and parts of North America

freed from malaria

Sweden and parts of North America

freed from malaria

Tunisia, Maldives and UAE

freed from malaria

Tunisia, Maldives and UAE

freed from malaria


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MALARIA PROGRAMME

199419941994

196619661966

194619461946

mid 19th centurymidmid 1919thth centurycentury

Lower malaria vectorial capacity

in temperate and sub-tropical areasLowerLower malaria malaria vectorialvectorial capacitycapacity

in in temperatetemperate and suband sub--tropical areastropical areas


MALARIA PROGRAMME


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SporozoitesSporozoitesSporozoitesSporozoitesHepatic phaseHepatic phaseHepatic phaseHepatic phaseInvading Invading Invading Invading ring stagering stagering stagering stageTrophozoiteTrophozoiteTrophozoiteTrophozoite

Sexual phaseSexual phaseSexual phaseSexual phaseGametocytesGametocytesGametocytesGametocytes

AsexualAsexualAsexualAsexualErythrocyticErythrocyticErythrocyticErythrocyticcyclecyclecyclecycleThe life cycle of the

malaria parasite,

Plasmodium

Non-Infected

Infected Disease Severe Death

Effective interventions are availableEffective interventions are available

Resolved Cured Cured

• Vector control

• Intermittent Preventive Therapy in pregnancy

• Chemoprophylaxis

• Early Diagnosis

• Appropriate Treatment

• Referral

• Hospital-based management


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Non-Infected

Infected Disease Severe Death

Need for new tools and technologies Need for new tools and technologies

Resolved Cured Cured

••New combination therapiesNew combination therapies

••Better rapid diagnostic testsBetter rapid diagnostic tests

••Better drug formulations Better drug formulations

••ITN:ITN: new long lasting new long lasting

••Insecticides: Insecticides: Safer & Safer &

longer residual effect longer residual effect

••Intermittent Rx: Intermittent Rx:

safer drugs in pregnancysafer drugs in pregnancy

••VaccinesVaccines

Current WHO recommendations for risk areas in malaria endemic countries

Green Green no prevention needed

BlueBlue type I prevention (anti-mosquito)

YellowYellow type II prevention (CQ)

OrangeOrange type III prevention (CQ+P)

RedRed type IV prevention (M, D or A-P)

Plus mosquitoPlus mosquito

bite preventionbite prevention


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Personal

protection

Insecticide treated

mosquito nets &

curtains

Now insecticides

are incorporated

into the synthesis of

the netting material

itself - LLNs

Can you see any problem? Can you see any problem?


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MALARIA PROGRAMME

Chemoprophylaxis for areas with high

falciparum transmission or high resistance

Chemoprophylaxis for areas with high Chemoprophylaxis for areas with high

falciparum transmission or high resistancefalciparum transmission or high resistance

WHO Recommended regimens

� Mefloquine 5mg/kg weekly

� Doxycycline 1.5 mg/kg daily

� Atovaquone proguanil *- 11-20 kg: One pediatric tab daily

- 21-30 kg: Two pediatric tabs daily

- 31-40 kg: Three paediatric tabs daily

- > 40 kg: One adult tablet daily

* start 1 day before departure and continue for 7 days after return

Additional regimen

� Primaquine off-label use

� 30 mg base daily has protective

efficacy above 85% against

P.falciparum and primary

infections with P.vivax

� Needs G6PD screening

JAMA 2007; 297: 2251-2263

Similar protective efficacy and effective against all Plasmodium species

Current WHO recommendations when to start & when to stop taking chemoprophylaxis

International Travel and Health (WHO, 2008)

mefloquine

chloroquineweekly

doxycycline

proguanil

chloroquine

When interruptedatovaquone-

proguanil

daily

exceptionally

4 weeks upon return

4 weeks

upon return

1 week

upon return

day

before arrival

1 week

before arrival

preferably 2-3 weeks

before departure

Chemo-

prophylaxisregimen

stopstart


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current guidelines & WHO recommendations

long-term travellers

no increased risks if tolerated in the short term, no accumulationmefloquine

risks lowproguanil

limited data > 12 months use, but reassuringdoxycycline

risks low, except retinal toxicity at cumulative dose of 100 g (3-5 yrs)chloroquine

In European countries use of limited duration (5 weeks, 3 months, 6 months, "many months", 1 year), in USA

unlimited duration

atovaquone-proguanil

long term use > 6 months

In sum: "Anything tolerated in the short term can most probably also be taken long-term"

Adherence -- Tolerability


MALARIA PROGRAMME

High risk group: pregnant womenHigh risk group: pregnant womenHigh risk group: pregnant women

In areas with low or unstable transmission

Acquired Immunity = Low

Clinical Illness

Severe Disease

Risk to Mother Risk to Fetus

• All pregnancies at risk

• Up to 60% fetal loss and 10% maternal deaths

• 50% maternal mortality with severe disease


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current guidelines & WHO recommendations

chemoprophylaxis use in special groups

proguanil

< 5 kg ??mefloquine

< 8 yrsdoxycycline

chloroquine

<11 kg

atovaquone-

proguanil

young children

breast feeding

2nd & 3rd

trimester pregnancy

1st

trimester pregnancy

Chemo-prophylaxis

= contra-indicated

= not recommended for lack of data

= safe

International Travel and Health (WHO, 2008)


MALARIA PROGRAMME

Chemoprophylaxis during pregnancy

and breastfeeding periodChemoprophylaxis during pregnancy Chemoprophylaxis during pregnancy

and breastfeeding periodand breastfeeding period

� Areas with P.vivax or CQ sensitive P.falciparum- Chloroquine weekly chemoprophylaxis

� Areas with P.vivax and P.falciparum and emerging CQ

resistance- Chloroquine + proguanil daily chemoprophylaxis

� Areas with high P.falciparum transmission or high levels

of resistance– Mefloquine weekly chemoprophylaxis (limited safety information in first

trimester)


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The clinical

presentation

of malaria

The clinical

presentation

of malaria

Fever (uncomplicated malaria)

Severe malaria

ANTIMALARIAL

TREATMENT

Cu

mu

lati

ve

Pro

ba

bil

ity

of

a

fata

l o

utc

om

e

t (hours)

Foundations of the Case Management Strategy

The earlier the treatment, the lower the probability of fatal outcome


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Plasmodium falciparumPlasmodium falciparum

Plasmoodium vivax

Malaria mortalityMalaria mortality

Malaria Rapid Diagnostic Tests (RDTs)

contact e-mail for

specific questions:

[email protected]


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Rapidly increasing

range of malaria RDT

products

Manufacturer Product

Access Bio Carestart Malaria

ACON laboratories Malaria Rapid Test Device

Alldiag Palutop

Ameritek dBest Malaria Rapid Test

Amgenix OnSight Malaria

Binax NOW-ICT

r-Biopharm MalaQuick (~NOW-ICT)

Bio-Quant Inc. One Step malaria Rapid Test

Biotech Trading Partners Malaria Pf-only Rapid Test

Cellabs Rapimal

Brittney Immu-Sure Malaria

Bio-Analytics C.A. Malaria Test

Core Diagnostics Core Malaria

Cortez Malaria P.f. RapiCard InstaTest CTK CTK Onsite

Diamed AG OptiMal

Fortress Diagnostics Malaria Test

Genelabs Assure Malaria

GlobaleMed Smart Check Malaria

Guangzhou Wondfo One Step Malaria

Human Gmbh Hexagon Malaria

Inbios

International Immunodiagnostics Malaria Test Card

J Mitra Advantage Malaria

KAT Medical KatQuick

Makro Medical MakroMAL

Merlin Labs Malaria Pf test

Omega Diagnostics Visitect malaria

Orchid Biomedical Systems Paracheck

Premier Medical Corporation First Response Malaria Antigen Test

R&R Marketing ICT Malaria

SDHO

Span Diagnostics ParaHIT

Standard Diagnostics SD Bioline Malaria

Syntillent ADI Malaria

Tashima

Trinity Biotech Uni-Gold Malaria

Unimed FirstSign / Paraview Malaria

Vision Biotech Malaria Pf

Zephyr Biomedical Systems Falcivax

~50 manufacturers with named products known to WHO

>50 million tests procured in 2007

Most endemic countries have no / weak regulations

Vulnerabilities of RDTs in the field

Cautions:

• Detect antigen, not parasites.

• (-) May reflect recent, not current,

parasitaemia.

• Degraded by excessive heat.

• Limited shelf life.

• Accuracy is dependent on technique used.


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Variation in results in published trials… e.g. ICT Malaria, ‘OptiMAL’: Sensitivity >90% in multiple trials, but…...

Sensitivity (% ) for P. falciparum (vs. microscopy)

ICT M alaria Pf, Pf/Pv 82-95 Iqbal et al 2001

82.6 Huong et al 2002

80.8 Stow et al 1999

74-90 W ongsrichanalai 1999

89 Gaye et al 1998

86.2 M ason et al 2002

66.1 Rubio et al 2001

84 Leke 1999

Sensitivity (% ) for P. falciparum (vs. microscopy)

'O ptiM AL' 80% Hernandez et al 2001

88.5 Jelinek et al. 1999

70.7 M ankhambo et al 2002

83 R icci et al 2000

49.7 Huong et al 2002

42.6 M ason et al 2002

81.3 Rubio et al 2001

Field trials…

All had poor sensitivity below 100 parasites per microlitre.

eg.


MALARIA PROGRAMME

Malaria diagnosisMalaria diagnosis

�Quality-assured confirmation of diagnosis with

microscopy before treatment

Exception:

– Patients with suspected severe malaria when blood slide

examination is not immediately possible


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MALARIA PROGRAMME

Treatment of uncomplicated

falciparum malaria


falciparum malaria

� Artemisinin-based combination therapies (ACT) are treatments of choice for all cases of uncomplicated falciparum malaria including:

– infants,

– people living with HIV/AIDS

– for home-based management of malaria

– pregnant women in the 2nd and 3rd trimesters

Exception:

• 1st trimester of pregnancy*

* use ACTs only if no alternative effective antimalarials


MALARIA PROGRAMME

� The following ACTs are recommended by WHO:– artemether-lumefantrine

– artesunate + amodiaquine

– artesunate + mefloquine

– artesunate + sulfadoxine-pyrimethamine

� 1st-line treatment based on therapeutic efficacy studies

in the country

� Response to treatment of travellers depends on the

origin of infection


falciparum malaria


falciparum malaria

95% cure rates in most studies

95% cure rates 95% cure rates

in in mostmost studiesstudies


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MALARIA PROGRAMME

Anti-relapse therapy in vivax malariaAntiAnti--relapse therapy in relapse therapy in vivaxvivax malariamalaria

� To achieve radical cure, relapses must be prevented by giving

primaquine.

� In low-transmission areas the benefits of deploying primaquine

are considered to exceed the risks.

� Primaquine in 0.25 mg/kg daily doses (adult daily dose of 15 mg)

should be given for 14 days - no evidence that shorter courses

are effective.

� P. vivax infections acquired in Indonesia and Oceania require

higher dose of primaquine for radical cure, i.e. 0.50 mg/kg

per day for 14 days


MALARIA PROGRAMME

Key points to rememberKey points to remember

1. No protective malaria "immunity" even after living many years without clinical attacks in endemic areas – be aware of the risk

2. Travel to endemic areas with insecticide-treated mosquito nets, preferably long-lasting

3. Start appropriate chemophrophylaxis as for short-term travellers, and continue for all the duration of exposure

4. Evaluate possibilities for access to early malaria diagnosis andprompt treatment at destination

5. Procure highly effective artemisinin-based combination therapy for stand-by emergency treatment of uncomplicated malaria

6. If febrile, report exposure to malaria risk to the treating clinician


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MALARIA PROGRAMME

Acknowledgements

David Bell, WHO

Western Pacific Region

Kamini Mendis, WHO


Aafje Rietveld , WHO


Contact email

to ask more specific

malaria questions:

[email protected]

Contact email

to ask more specific

malaria questions:

[email protected]

Many thanks for your kind attentionMany thanks for your kind attention

Documents

How to protect yourself against malaria · PDF fileDorling D Worldmapper. PLoS Med 4 (1), 2007 4 | Mine Action Technology Workshop | 10 September 2008 GLOBAL MALARIA PROGRAMME Global